Cerebrospinal Fluid Total Protein Reference Intervals Derived from 20 Years of Patient Data

Abstract

Background: Reference intervals are vital for interpretation of laboratory results. Many existing reference intervals for cerebrospinal fluid total protein (CSF-TP) are derived from old literature because of the invasive nature of sampling. The objective of this study was to determine reference intervals for CSF-TP using available patient data.

Methods: Twenty years of hospital database information was mined for previously reported CSF-TP results. Associated demographic, laboratory, and clinical diagnosis (International Classification of Diseases 9/10 codes) details were extracted. CSF-TP results included 3 different analytical platforms: the Siemens Vista 1500, Beckman Lx20, and Roche Hitachi 917. From an initial data set of 19591 samples, the following exclusion criteria were applied: incomplete data, white blood cells (WBCs) >5 × 10⁶/L, red blood cells (RBCs) >50 × 10⁶/L, and glucose <2.5 mmol/L. Patient charts were reviewed in detail to exclude 60 different conditions for which increases in CSF-TP would be expected. A total of 6068 samples were included; 63% of the samples were from females. Continuous reference intervals were determined using quantile regression. Age- and sex-partitioned intervals were established using the quantile regression equation and splitting age-groups into 5-year bins.

Results: CSF-TP showed a marked age dependence, and males had significantly higher CSF-TP than females across all ages. CSF-TP results from the 3 different instruments and manufacturers showed small (approximately 0.04 g/L), but statistically significant, differences. CSF-TP showed weak, but again statistically significant, correlation with WBC and RBC but was independent of serum total protein and creatinine.

Conclusions: The age dependence of CSF-TP supports that age-partitioned reference intervals will be more accurate than a single cutoff, particularly in patients with advancing age.